Our aim is to develop a simple and effective method for the delivery of tetanus vaccines by non-invasive application of expression vectors onto the skin. The hypothesis is that the expression of tetanus toxin C-fragment in the outer layer of skin can induce systemic immune responses against the toxin. We have demonstrated that animals could be vaccinated by non-invasive application of expression vectors encoding specific antigens onto the skin. These studies will further develop skin-targeted non-invasive vaccines, and specifically determine whether this novel approach for the delivery of vaccines can mobilize the immune repertoire toward a beneficial immune protection against tetanus. In this project, non-invasive vaccination onto the skin (NIVS) against tetanus will be developed by formulating DNA/adenovirus and DNA/liposome complexes into skin-targeted non-invasive tetanus vaccines. Efficacy of NIVS will be compared with those induced by other means. The overall goal of these experiments is to determine whether tetanus vaccines can be effectively delivered by non-invasive application of DNA onto the skin that requires a lower level of skill in a needle-free manner. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE